Current Hepatology Reports

Cirrhotic cardiomyopathy (CCM) is a clinical entity that reflects the maladaptive responses of the heart to advanced chronic liver disease. With the recent developments in this field, this review details the most up to date knowledge about the pathogenesis of CCM, recent changes in its diagnostic criteria, and its clinical relevance. Advances in echocardiographic techniques over the last several years and recent research have highlighted the high prevalence of CCM approaching 35% and demonstrated adverse impact of CCM on clinical outcomes following transjugular intrahepatic portosystemic shunting (TIPS) and liver transplantation (LT). The diagnostic criteria for cirrhotic cardiomyopathy have evolved with advancements in echocardiographic techniques allowing for precise and perhaps timely identification of those with subclinical cardiac impairment. CCM increases the risk for adverse outcomes in patients with cirrhosis and liver transplant recipients. Future studies are needed to identify subgroups of patients at highest risk for cirrhotic cardiomyopathy, the frequency and duration of monitoring for those with CCM, and potential therapeutics for patients with cirrhosis and liver transplant who have been diagnosed with cirrhotic cardiomyopathy.

The growing epidemic of obesity has led to an increase in the number of patients developing end-stage liver disease related to nonalcoholic steatohepatitis (NASH). In fact, NASH is now the second-leading etiology for liver transplantation in the USA. In this context, interest is growing in understanding the outcomes of liver transplantation in patients with NASH. Current data suggest that the short- and medium-term outcomes for NASH patients post-transplantation are not different from those for other recipients. Nevertheless, patients with NASH and diabetes may have higher risk post-transplantation for de novo diabetes. Caregivers must be vigilant post-transplant for the development of de novo diabetes regardless of their pre-transplant status. NASH patients also seem to have a lower functional status post-transplant. There are conflicting data regarding the outcome of morbidly obese patients with NASH who undergo liver transplantation. The pre-transplant management of these patients with surgical weight loss is reported, but caution must be exercised in considering them for transplant.

This review summarizes the pathophysiology of portal hypertension, outcome data through the years supporting the use of TIPS in refractory ascites (RA) and hepatic hydrothorax (HH), and considerations for ideal TIPS candidates. Advances in stent technology over the last three decades have dramatically improved both quality of life and survival for patients with RA and HH. Importantly, the advent of controlled-expansion, covered stents has reduced the incidence of post-TIPS hepatic encephalopathy (HE) and mortality rates. Controlled-expansion covered stents are now the guideline-recommended device for patients undergoing TIPS. Prospective trials including these newer TIPS recipients are still needed to determine ideal stent diameter, effective intra-operative portosystemic gradient cutoffs, and utility of pharmacologic HE prophylaxis for the indications of RA and/or HH.

Hepatoblastoma and hepatocellular carcinoma are rare pediatric tumors. We review the significant advances in hepatoblastoma and pediatric hepatocellular carcinoma prognosis and treatment. International pathologic classification and risk stratification have been extensively reviewed and redefined for hepatoblastoma via international collaborative analyses of an international hepatoblastoma database. International trials have identified patients for whom (1) no adjuvant chemotherapy is indicated, (2) neoadjuvant chemotherapy improves resectability and survival, and (3) intensified therapy improves survival (for patients with metastatic disease). Hepatocellular carcinoma studies highlight the poor prognosis for patients with nonlocalized disease emphasizing the need for future collaborative efforts exploring molecular characteristics and novel therapeutics. Recent advances have significantly improved treatment of hepatoblastoma by implementing a consensus international pathologic classification and risk stratification and identification of higher risk biological features. Advances in pediatric hepatocellular carcinoma treatment lag behind hepatoblastoma. The Pediatric Hepatic International Tumor Trial (PHITT) will focus on decreasing long-term toxicity, improving outcomes, providing surgical guidelines, and advancing the knowledge of the biology of hepatoblastoma and hepatocellular carcinoma.

The review details recent literature reports regarding Hepatitis B Virus (HBV) and, in particular, Hepatitis B prevalence/incidence in incarcerated populations around the world. Furthermore, the review will summarize the national/international guidelines regarding HBV and look at diagnosis, vaccination, treatment, and linkage to care after release. HBV affects prisoners at a much higher rate than the general populations. Many who are at increased risk for HBV infection are also at increased risk for incarceration. Incarcerated settings also have higher rates of HBV transmission. Incarcerated individuals should be immunized if they are not already immune to HBV. Increased access to safe injecting and tattoo paraphernalia, condoms, and personal hygiene equipment could reduce the spread of HBV and other blood-borne and sexually transmitted infections. Future research should focus on ways to prevent the spread of HBV and similar viruses in incarcerated settings in order to protect incarcerated individuals and the general public. Research on effective linkage to community HBV care following release is needed.

Occult hepatitis B infection refers to the presence of replication-competent hepatitis B virus despite the lack of hepatitis B surface antigen due to epigenetic or immune control. Risk factors for occult hepatitis B infection include sex work, blood transfusion, hemodialysis, and liver transplantation. Historically, the recognition of occult hepatitis B infection has been important in preventing reactivation of hepatitis B infection and mortality in those receiving treatment for HIV and hepatitis C virus along with those receiving immunosuppressive therapy. Recognition of occult hepatitis B infection has increased and continues to evolve with improved detection methods in both serum and liver tissue to identify HBV DNA. Advancements in the understanding of genetic variations of hepatitis B have also contributed to the differentiation of overt versus occult hepatitis B infection. More recent research has contributed to the debate that occult hepatitis B infection may play a role in clinical outcomes such as chronic liver disease and hepatocellular carcinoma. With enhanced awareness of occult hepatitis B and improved methods for detection of HBV DNA and hepatitis B surface antigen, future studies understanding the natural history will shape policy regarding therapeutics and preventive strategies to prevent occult hepatitis B–related morbidity and mortality.

Cholangiocarcinoma is a devastating, unpredictable complication of large duct primary sclerosing cholangitis (PSC), which occurs in 5–15% of patients. The aim of this review is to discuss whether dominant strictures (DS) occurring in the larger bile ducts in PSC are a risk factor for the development of cholangiocarcinoma. The development of DS is related to specific genetic polymorphisms affecting the innate immune system and the microbiome. In a recent study, the mean survival of PSC patients with DS was much worse (13.7 years) than for those without a DS (23 years). Survival difference was related to a 26% risk of cholangiocarcinoma, which developed only in those with DS. Half of the patients with cholangiocarcinoma presented within 4 months of the diagnosis of PSC. In another study, the risk of developing cholangiocarcinoma was directly related to the presence of underlying IBD, although this remains controversial. Efforts are being made towards surveying for cholangiocarcinoma including magnetic resonance imaging, endoscopic surveillance and serum tumour markers, but so far, an effective surveillance strategy has not been identified. DS should be treated endoscopically in the setting of symptoms, and there is limited evidence to suggest this may impact protectively on progression to cholangiocarcinoma. It is established that the presence of symptomatic DS occurring in the larger bile ducts in PSC can be the first presentation of cholangiocarcinoma. There is an increasing body of evidence that even when proven to be benign, dominant biliary strictures predispose to the future development of cholangiocarcinoma. Regular surveillance should be targeted at this selected high-risk group of PSC patients.

Idiopathic non-cirrhotic portal hypertension is described with a very heterogeneous terminology depending on the geographic origin of the patients and on the possible underlying causes of the disease. We aim here to review the current nomenclature and to the pathophysiological origins of this entity. In the past, a relevant number of definitions of this condition have been used in the literature, suggesting the presence of several distinct diseases. However, recent findings strongly suggest that there are some common denominators for this disease. Therefore, efforts should be made to develop a unified terminology encompassing the very essential features from clinical, histologic, imaging, laboratory and elastographic data. These findings suggest that the common localization of the disease is the portal and the sinusoidal compartment of the liver; therefore, a novel definition should be elaborated.

Viral hepatitis caused by various hepatotropic viruses (Hepatitis A, B, C, and E) is common in developing countries and continues to cause significant morbidity and mortality. The liver is the largest organ of the body with various metabolic functions. Patients with acute and chronic viral hepatitis often have altered metabolism leading to decreased food intake and malnutrition. The presence of protein and calorie malnutrition in these patients may increase morbidity and mortality. Early identification and prompt treatment of malnutrition improve prognosis and overall survival. The aim of this review was to address the metabolic role of the liver, and the prevalence, and etiopathogenesis of various micro and macronutrient deficiencies in patients with viral hepatitis. The role of nutrition in specific high-risk groups has also been outlined. Patients with viral hepatitis can have both micro and macronutrient deficiency. Reduced dietary intake and altered metabolic state are the leading causes of malnutrition. Early diagnosis and management of malnutrition in viral hepatitis are crucial to reduce morbidity and mortality. Provision should be made to educate public leaders, primary health care workers, and treating physicians to reduce the prevalence of malnutrition.

In this review, we examine the interaction between the metabolic syndrome (MS) and non-alcoholic fatty liver disease (NAFLD) and describe the impact of the features of MS on the most worrisome complications of non-alcoholic steatohepatitis (NASH), (cirrhosis, hepatocellular carcinoma) and, ultimately, on liver-related, cardiovascular, and overall mortality. Insulin resistance, obesity, and dyslipidemia in a pro-inflammatory environment have a causal role in hepatic fibrogenesis and oncogenesis in NAFLD patients. Natural history, longitudinal studies confirm the conditions linked to MS as independent predictors of overall-, cardiovascular-, and liver-related mortality. Dysmetabolic factors stemming from insulin resistance play a key role in liver damage progression. Obesity, type 2 diabetes (T2DM), dyslipidemia, and arterial hypertension are independent predictors of liver fibrosis and cirrhosis; furthermore, obesity and T2DM play a key role in the development of hepatocellular carcinoma both in cirrhotic and non-cirrhotic NASH patients.